Evaluation Of Hemostasis Research Articles

Efficacy of a RADA-16 peptide hydrogel versus chitosan-based polymer in improving patient comfort during postoperative debridement: A randomized controlled trial.

Bioresorbable nasal packing is associated with a decreased incidence of adhesions and bleeding postoperatively after endoscopic sinus surgery (ESS). However, discomfort during postoperative debridement is still a major area of concern for patients. Our objective was to compare the efficacy of a peptide hydrogel to that of a chitosan-based polymer in reducing pain during debridement after ESS. A prospective, multicenter, randomized, blinded trial was conducted in adults undergoing bilateral total ethmoidectomy for chronic rhinosinusitis. Participants served as their own controls with each subject receiving the hydrogel in a randomized ethmoid cavity and chitosan-based polymer in the contralateral ethmoid cavity. Participants were evaluated at 1, 4, and 12weeks postoperatively. Pain during debridement as well as endoscopic evaluation of mucosal healing and hemostasis were measured. Thirty patients who underwent ESS were included in this trial. During the week 1 postoperative debridement, patients reported significantly less pain on the hydrogel-treated side compared to the chitosan-based polymer-treated side. There were no significant differences in bleeding severity, Lund-Kennedy scores, debridement time, or need for further intervention between the two groups. This study demonstrated the efficacy of a peptide hydrogel inminimizing pain during postoperative debridement.

Hemostasis Testing in the Emergency Department: A Narrative Review.

Routine laboratory screening is typically performed at initial evaluation of the vast majority of presentations to the emergency department (ED). These laboratory results are crucial to the diagnostic process, as they may influence up to 70% of clinical decisions. However, despite the usefulness of biological assessments, many tests performed are inappropriate or of doubtful clinical relevance. This overutilization rate of laboratory testing in hospitals, which represents a significant medical-economic burden, ranges from 20 to 67%, with coagulation tests at the top of the list. While reviews frequently focus on nonintensive care units, there are few published assessments of emergency-specific interventions or guidelines/guidance to date. The aim of this review is to highlight current recommendations for hemostasis evaluation in the emergency setting with a specific analysis of common situations leading to ED admissions, such as suspected venous thrombosis or severe bleeding. We revisit the evidence related to the assessment of patient's hemostatic capacity based on comprehensive history taking and physical examination as well as best practice recommendations for blood sample collection to ensure the reliability of results. This review also includes an examination of various currently available point of care tests and a comprehensive discussion on indications, limitations, and interpretation of these tests.

The hemostatic performance and mechanism of palygorskite with structural regulate by oxalic acid gradient leaching

Palygorskite (Pal) is a naturally available one-dimensional clay mineral, featuring rod-shaped morphology, nanoporous structure, permanent negative charges as well as abundant surface hydroxyl groups, exhibiting promising potential as a natural hemostatic material. In this study, the hemostatic performance and mechanisms of Pal were systematically investigated based on the structural regulate induced by oxalic acid (OA) gradient leaching from perspectives of structure, surface attributes and ion release. In vitro and in vivo hemostasis evaluation showed that Pal with OA leaching for 1 h exhibited a superior blood procoagulant effect compared with the raw Pal as well as the others leached for prolonging time. This phenomenon might be ascribed to the synergistic effect of the intact nanorod-like morphology, the increase in the surface negative charge, the release of metal ions (Fe3+ and Mg2+), and the improved blood affinity, which promoted the intrinsic coagulation pathway, the fibrinogenesis and the adhesion of blood cells, thereby accelerating the formation of robust blood clots. This work is expected to provide experimental and theoretical basis for the construction of hemostatic biomaterials based on clay minerals.

T-TAS® 01 as a new tool for the evaluation of hemostasis in thrombocytopenic patients after platelet transfusion.

Current laboratory tests fail to evaluate the hemostatic function of platelets in patients with thrombocytopenia. We investigated the use of the Total Thrombus-Formation Analysis System (T-TAS® 01 [Fujimori Kogyo Co, Tokyo, Japan]) to evaluate hemostasis under conditions of experimental thrombocytopenia, and in patients before and after platelet transfusion. Specific T-TAS 01 chips, for thrombocytopenic conditions, were used. The area under the curve (AUC) and occlusion time (OT, min) were measured in: (i) experimentally induced thrombocytopenia (183±15 to 6.3±1.2×103 platelets/μL) in blood samples from healthy donors (No.=13), and (ii) blood from oncohematological thrombocytopenic patients (No.=48), before and after platelet transfusion. The influences of hematocrit and number of transfusions were analyzed in these patients. Progressive reductions of AUC and prolongations of OT related significantly to decreasing platelet counts (p<0.05 for all) in experimental thrombocytopenia. In samples from thrombocytopenic patients, platelet counts, AUC and OT were, respectively, 10.8±0.6×103/μL, 175.2±59, and 27.2±1 min before transfusion; and 22±1.5×103/μL, 400.8±83 and 22.9±1.5 min after platelet transfusion (p<0.01 for all). A hematocrit below 25% or exposure to ten or more previous platelet transfusions had a negative impact on the T-TAS 01 performance in patients. In vitro correction of the hematocrit improved the hemostatic response in thrombocytopenic patients. T-TAS 01 measurements were sensitive to low platelet counts in the experimental setting. The technology was sensitive to evaluate the hemostatic capacity of platelet transfusions. Exposure to multiple medications, repeated platelet transfusions and lower hematocrits may interfere with the hemostatic performance in oncohematological patients with thrombocytopenia.

Thrombin generation and all-cause mortality in The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Introduction: Thrombin generation assay (TGA) is a laboratory method that provides the global evaluation of hemostasis. The association between thrombin generation and all-cause mortality is poorly investigated and results are contradictory. This study evaluated whether TGA parameters are associated with all-cause mortality in a prospective cohort. Methods: This study was conducted in 2,588 participants enrolled at baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). TGA was performed using the Calibrated Automated Thrombogram (CAT) method, and its parameters lagtime, time-to-peak, peak, Endogenous Thrombin Potential (ETP) and normalized ETP (nETP) were evaluated according to the reference interval (RI). The association between TGA parameters and all-cause mortality was estimated by Cox regression and adjusted for confounders. Results: The mean follow-up time was 6.6 ± 2.7 years and 85 deaths occurred. After adjustment, time-to-peak values above the RI at low and high tissue factor (TF) concentrations were associated with higher risk of death [HR = 2.45 (95 % CI: 1.17–5.13) and HR = 2.24 (95 % CI: 1.02–4.93), respectively] and nETP and peak values below RI at high TF concentration were associated with higher risk of death [HR = 3.85 (95 % CI: 1.39–10.68) and HR = 2.56 (95 % CI: 1.17–5.61), respectively]. Conclusions: Delayed thrombin generation was associated with higher risk of all-cause mortality.

Monitoring of Hemostatic Status and Treatment Response in Von Willebrand Disease Using a Microchip Flow Chamber Assay

Introduction: Von Willebrand factor (VWF) carries out its hemostatic roles by interacting with both platelets and FVIII, and its appropriate active multimeric conformation is strongly affected by blood flow shear. Our aim was to assess the hemostatic status and the response to treatments in VW disease (VWD) using a flow chamber-based thrombus formation analysis system (T-TAS ®, Zacros) that allows evaluation of both primary and secondary hemostasis in a scenario closer to in vivo conditions. Methods: Blood samples from patients diagnosed with VWD type 1 (n=3), type 2A (n=2), type 2B (n=1) and type 3 (n=8, two of them with inhibitory antibodies) were collected before and after in vivo administration of the prescribed treatment with desmopressin (DDAVP ®) or plasma-derived (pd)VWF/FVIII concentrates (Table-1). The effect of ex vivo administration of 100, 150 and 300 IU/dL of pdVWF/FVIII (Fanhdi ®, Grifols) was also evaluated. Thrombus formation analysis was performed according to the manufacturer's standardized protocols: Blood samples collected in tubes containing BAPA (inhibitor of FXa and thrombin) were loaded onto type-1 collagen-coated platelet (PL)-chips to assess platelet-dependent thrombus formation. Citrated blood samples were recalcified in presence of CTI and loaded onto collagen/tissue factor-coated atherome (AR)-chips to assess thrombus formation mediated by both platelet and coagulation activation. An optimized flow rate is automatically adjusted for each chip. Area under the flow-pressure curve (AUC) values were collected. Platelet count, fibrinogen levels, prothrombin time (PT), activated partial thromboplastin time (aPTT), aPTT ratio, antigenic VWF (VWF:Ag), VWF activity by recombinant GPIb binding assay (VWF:GPIbR) and FVIII activity (FVIII:C) were also analyzed. Results: All VWD patient samples tested, including type-1 patients, showed a deficient platelet function (PL_AUC) and a reduced coagulation-dependent thrombus formation (AR_AUC) prior to treatment (Table-1). VWD type-1 responded to desmopressin with a high increase of FVIII activity (FVIII:C &amp;gt;200%) and normalization of VWF activity (VWF:GPIbR &amp;gt;100%) and AUC levels. Treatment with pdVWF/FVIII increased VWF:GPIbR levels (&amp;gt;60% after treatment) in all cases, but failed to completely normalize the AUC values, which showed a slight increase (Table-1). A high correlation (r&amp;gt;0.8) was observed between plasma levels of VWF or FVIII activity and AUC values obtained both before and after treatment Ex vivo administration of pdVWF/FVIIIa resulted in a concentration-dependent increased of PL_ and AR_AUC, with values within the normal range at the highest dose tested (300 IU/dL, equivalent to 150 IU/kg) in all cases, except for VWD type-3 samples with inhibitor and for VWD type-2B sample with PL-chip assay (Figure-1). Conclusions: Monitoring treatment efficacy in VWD using a flow chamber-based thrombus formation analysis system could be a reliable and standardized method to assess the response to desmopressin and pdVWF/FVIII concentrates in patients with VWD, allowing an optimal personalized therapeutic dosing and a better prevention of bleeding episodes in these patients. Funding: Grifols; Zacros; Fundación Rodríguez Pascual; Instituto de Salud Carlos III (ISCIII) (PI22/01461), co-funded by the European Union.

Low Rebleed Incidence with Eptacog Beta Treatment through 24 and 48 Hours in Children (

Introduction Persons with hemophilia A or B and inhibitors (PwHABI) who are not on prophylaxis may have high rates of bleeding, and, if not treated effectively, may have significant morbidity related to rebleeding. Dosing strategies of bypassing agents (BPAs) are variable in clinical practice, and following a period of initial bleed control, rebleeding may occur. The development of additional bypassing agents that can minimize the incidence of rebleeding in this patient population is an important medical need. Eptacog beta is a recombinant activated human factor VII approved in the US and Mexico (Sevenfact®, 2020), as well as the EU and UK (Cevenfacta®, 2022) as a BPA for the treatment of bleeding episodes (BEs) in PwHABI aged 12 years and older using two initial dose regimens (IDRs) of 75 or 225 µg/kg. In the EU and UK, eptacog beta is also indicated for preventing bleeding in the setting of surgery and other invasive procedures. Approval in the US and Mexico was based on demonstrated efficacy in the pivotal phase 3 PERSEPT 1 trial (NCT02020369), which included 27 adolescent and adult PwHABI who treated 465 mild or moderate BEs. Bleed resolution at 24 hours post-initial infusion was 96.7% and 99.5% for 75 and 225 µg/kg IDRs, respectively, with a single bleed recurrence observed before 24 hours. The subsequent phase 3 PERSEPT 2 trial (NCT02448680) enrolled 25 PwHABI &amp;lt;12 years of age who treated 546 mild or moderate BEs. Bleed resolution at 24 hours post-initial infusion in these pediatric patients was 97.4% and 98.0% for 75 and 225 µg/kg IDRs, respectively. The objective of this analysis is to evaluate the incidence of rebleeding when treating mild or moderate BEs in PwHABI &amp;lt;12 years of age with eptacog beta during PERSEPT 2 at 24 and 48 hours post-initial dose. Methods PwHABI in PERSEPT 2 were randomized to either the 75 or the 225 µg/kg IDR to treat BEs and were crossed over to the alternate IDR every 3 months. No subjects in PERSEPT 2 were using prophylaxis. Subjects assigned to the 75 µg/kg IDR treated BEs with initial doses of 75 µg/kg eptacog beta followed by 75 µg/kg q3h as needed. Subjects assigned to the 225 µg/kg IDR treated BEs with an initial 225 µg/kg eptacog beta dose, followed after 9 hours by 75 µg/kg q3h as needed. Mild or moderate BE treatment success at a given time point was assessed by the patient or caregiver and was defined as obtaining a hemostasis evaluation of “excellent” or “good” on a 4-point scale with no additional eptacog beta being infused, no alternative hemostatic agents or blood products being used, and no increase in pain following the first “excellent” or “good” assessment. For this analysis, a BE was considered a rebleed if occurring at the same anatomical location as the original bleed, and within 24 or 48 hours of the initial infusion for the original bleed. Results During the study, subjects treated 546 BEs. Nine rebleeds occurred among 4 of the 25 children within 24 hours, and 13 rebleeds occurred among 6 children within 48 hours. The rebleed incidence and 95% confidence intervals (CIs) through 24 hours was 1.3% [95% CI: 0.0%, 3.6%] for the 75 µg/kg IDR and 2.0% [95% CI: 0.0%, 3.9%] for the 225 µg/kg IDR. The corresponding rebleed incidence and 95% CIs through 48 hours for the 75 and 225 µg/kg IDRs were 2.1% [95% CI: 0.0%, 4.5%] and 2.6% [95% CI: 0.4%, 4.9%], respectively. The differences in rebleed incidence between the two IDRs were not statistically significant at either 24 or 48 hours (Figure 1). The overall rebleed incidence in PERSEPT 2 was 1.6% [95% CI: 0.0%, 3.7%] through 24 hours and 2.4% [95% CI: 0.2%, 4.5%] through 48 hours. No treatment-related adverse events or thrombotic complications were observed. Conclusions Eptacog beta demonstrated a low overall incidence of rebleeding through 24 hours (1.6%) and 48 hours (2.4%) in PwHABI &amp;lt;12 years of age during PERSEPT 2. Rebleeding was similarly low for either IDR at both time points. These findings align with those previously reported for PERSEPT 1 in adolescent and adult patients. Combined with the high efficacy at 24 hours (&amp;gt;96%) observed in both trials and both IDRs, these results suggest that eptacog beta can provide clinicians and caregivers with a treatment option that can establish and maintain hemostatic control of mild or moderate BEs in PwHABI of all ages.

PB0087 Use of Viscoelastic Tests in the Intensive Care Unit for the Evaluation of Haemostasis in SARS-COV-2 Infection

PB0087 Use of Viscoelastic Tests in the Intensive Care Unit for the Evaluation of Haemostasis in SARS-COV-2 Infection

Plasmic hemostasis evaluation by thrombodynamics in individuals booster dose vaccination against SARS-CoV-2

Plasmic hemostasis evaluation by thrombodynamics in individuals booster dose vaccination against SARS-CoV-2

Evaluation of Haemostasis in Dogs Affected by Resectable Malignancy

Dogs with neoplasm are at risk of thrombosis, yet there is no information on the haemostatic alterations that may result from the surgeries performed to remove neoplastic masses. The aim of this study was to observe the characteristics of haemostasis in dogs undergoing surgery to remove a malignancy by means of rotational thromboelastometry and thrombin generation. Haemostasis was assessed immediately before surgery (T0), 24 h after surgery (T1), and two weeks after surgery (T2). Statistically significant differences were found between the thromboelastometric parameters at T0 vs. T1, with increases observed in MCF, the α angle, and G parameters in the ex-TEM and in-TEM profiles. In the thromboelastometric analysis performed after surgery differences were identified between T1 and T2, with a decrease observed in parameters such as CFT, MCF, the α angle, and G. Between T0 and T2, only a significant decrease in CT was detected in the fib-TEM profile. No differences were found in the comparison among the results obtained via thrombin generation. In dogs with resectable malignancies, the surgeries performed to remove cancer affected coagulation, causing a tendency towards hypercoagulability. The interference with coagulation was transient, and 2 weeks after surgery, the thromboelatometric results returned to those obtained before surgery (T0).

Preparation of Nile tilapia skin collagen powder by low-temperature and comprehensive evaluation of hemostasis and wound healing.

Nile tilapia (hereinafter referred to as tilapia) is a species with high economic value and extensive cultivation. In this study, the low-temperature Nile tilapia skin collagen powder (TSCP) was prepared by liquid nitrogen freeze pulverization. After physical and chemical analysis of its properties, it was found that its characteristics were similar to those of type I collagen. The three-dimensional helix structure of protein peptide is good and non denatured. It shows that cryogenic temperature guarantees the activity of TSCP. In addition, TSCP has good biocompatibility. Specifically, it has good blood compatibility, lacks cytotoxicity, will not cause intradermal stimulation and acute systemic toxicity, and has no obvious rejection after implantation. In the rat liver hemorrhage model and wound repair model, compared with the commercially available bovine collagen powder (BSCP), TSCP has better blood coagulation ability: the shortest hemostatic time (135 s) and wound healing efficiency: the wound healing is obvious on the 14th day. The results of this study indicate that the TSCP is an ideal candidate for hemostatic agents and wound healing dressings.

Eptacog Beta (rFVIIa) Has a Low Incidence of Spontaneous Rebleeding through 24 and 48 Hours in Adult and Adolescent Patients with Hemophilia A or B with Inhibitors

Introduction Bypassing agents (BPAs [ie, recombinant FVIIa (rFVIIa) or activated prothrombin complex concentrate]) are the primary treatment option to control breakthrough bleeding episodes (BEs) in persons with hemophilia A or B with inhibitors (PwHABI). BPAs can have variable efficacy that may lead to rebleeding following initial successful hemostasis; this can result in additional product usage for rebleed treatment or prevention, delayed recovery, and possible re-hospitalization or prolonged hospitalization. Eptacog beta (SEVENFACT®; HEMA Biologics and LFB) is a human rFVIIa that is approved for use in the US for the treatment and control of BEs in PwHABI (aged ≥12 years). In the PERSEPT 1 trial (PwHABI aged ≥12 years), 2 dosing regimens were investigated for the treatment of mild/moderate BEs: the 225µg/kg initial dose regimen (IDR) and the 75µg/kg IDR (Fig 1). Efficacy at 12h was 91% (225µg/kg IDR) and 82% (75µg/kg IDR); efficacy at 24h was 99.5% (225µg/kg IDR) and 96.7% (75µg/kg IDR). The median number of doses to treat a mild/moderate BE were 1 (225µg/kg IDR) and 2 (75µg/kg IDR). No thrombotic events were observed. Aims The aim of this analysis is to examine the incidence of rebleeding in PwHABI ≥12 years when using eptacog beta to treat mild/moderate BEs. Methods PERSEPT 1 (NCT02020369) was a prospective, randomized, crossover trial that investigated eptacog beta (225µg/kg and 75µg/kg IDRs). Informed consent/assent was obtained. Subjects with hemophilia A or B with inhibitors (who were not using prophylaxis) received an initial dose of eptacog beta (225µg/kg or 75µg/kg) for BE treatment followed by 75µg/kg doses at predefined intervals determined by clinical response (Fig. 1). Treatment success for mild/moderate BEs was defined as a patient-reported hemostasis evaluation of excellent or good (using a predefined 4-point scale) with no use of additional eptacog beta, alternative hemostatic agents or blood products, and no increase in pain following the first excellent or good assessment. Rebleeding through the first 24h was reported by the subject and defined as a BE in the same anatomical location after an initial excellent/good assessment. Rebleeding through 48h was an exploratory analysis of all BE data on a subject-by-subject basis: if subsequent bleeds occurred in the same anatomical location, and the initial doses of eptacog beta for each BE were administered within 48h of each other, then the latter BE was considered a rebleed. Results Twenty-seven subjects (aged 12-54) enrolled in PERSEPT 1; 465 mild/moderate bleeds were reported. Subjects used the same IDR to treat both the initial BE and the rebleed. All rebleeds were reported as mild/moderate. During the first 24h of BE treatment a single rebleed was reported (1/465; 0.2% incidence; Table 1). During the first 48h following initial treatment of a BE, this intention-to-treat analysis identified 19 rebleeds at the same anatomical location (incidence of 4.1%) in 11 subjects; the incidence by IDR is shown in Table 1. The majority (91%) of rebleeds through 48h treated with the 225µg/kg IDR were controlled with a single 225µg/kg dose (1 rebleed required an additional 75 µg/kg dose); 50% (4/8) of those treated with the 75µg/kg IDR required a single 75µg/kg dose to achieve bleed control (the remainder required 2 or 3 75µg/kg doses). All rebleeds achieved hemostasis by 12h and none required a hospital/HTC visit. A second analysis that excluded 2 rebleeds in 1 subject who was removed from the trial due to lack of treatment adherence and 1 rebleed in a 2nd subject that was a result of traumatic reinjury, resulted in a 3.4% incidence of rebleeding during the first 48h (Table 1). Conclusion Eptacog beta has a low incidence of rebleeding through 24h (0.2%) and 48h (4.1%) as observed in PERSEPT 1; in the few cases where rebleeding did occur, the majority of rebleeds required a single dose of only eptacog beta to achieve hemostasis and none required a hospital/HTC visit. In hemophilia without inhibitors, it is typical to be able to administer a minimal number of FVIII/FIX doses to control a BE and have a low risk of rebleeding; the data reported in PERSEPT 1 suggest a similar outcome for the control of mild/moderate BEs in inhibitor patients with eptacog beta. These new data may permit providers to make informed treatment decisions for inhibitor patients to reduce or avoid the possibility of rebleeding without the need for additional doses and their associated cost. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Eptacog Beta Efficacy in Treating Mild or Moderate Bleeds in Target Joints of Individuals with Hemophilia A or B and Inhibitors in PERSEPT 1

Introduction Recurrent bleeding in the same joint of a patient with hemophilia can lead to painful and chronic inflammation of the synovium, joint swelling, reduced range of motion, and in the long term joint arthropathy and irreversible joint damage. Early bleed resolution in the susceptible joint (known as a target joint) is thought to be crucial for preventing joint arthropathy and other incapacitating sequelae, and thus ultimately preserving joint function and health in persons with hemophilia. Eptacog beta was FDA-approved in 2020 as a recombinant activated human factor VII for the treatment and control of bleeding episodes (BEs) in persons with hemophilia A or B and inhibitors (PwHABI) ages 12 years and older using two initial dose regimens (IDRs) of 75 or 225 µg/kg eptacog beta that were shown to be safe and efficacious. The pivotal phase 3 trial (PERSEPT 1; NCT02020369) included 27 PwHABI ages 12 to 54 years who treated 465 mild or moderate BEs, with treatment success proportions at 12 hours post-initial infusion of 82% and 91% for 75 and 225 µg/kg IDRs, respectively. Objective To evaluate eptacog beta efficacy when treating target and non-target joint BEs in PwHABI from PERSEPT 1, at 12 and 24 hours post-initial dose of eptacog beta. Methods PERSEPT 1 was a global, multicenter, open-label, prospective phase 3 trial using a crossover design (Wang et al., Haemophilia 23, pp. 832-43 [2017]). PwHABI who were not using prophylaxis were randomized to either the 75 or the 225 µg/kg IDR to treat BEs, and were crossed over to the alternate IDR every 3 months. Subjects in the 75 µg/kg IDR treated BEs with initial doses of 75 µg/kg eptacog beta followed by 75 µg/kg q3h as needed. Subjects in the 225 µg/kg IDR treated BEs with an initial 225 µg/kg eptacog beta dose, followed after 9 hours by 75 µg/kg q3h as needed. Mild or moderate BE treatment success at a given timepoint was defined as obtaining a hemostasis evaluation of "excellent" or "good" on a 4-point scale ("excellent" or "good" indicating hemostatic efficacy; "moderate" or "none" indicating lack of efficacy) with no additional eptacog beta being infused, no alternative hemostatic agents or blood products being used, and no increase in pain following the first "excellent" or "good" assessment. A target joint was defined in this trial as a joint in which recurrent bleeding had occurred on 4 or more occasions during the previous 6 months, or a joint in which 20 lifetime BEs had occurred. Results Twenty-seven PwHABI treated 396 mild or moderate joint BEs in PERSEPT 1; 17 of these subjects had been previously diagnosed with target joints. Of the 396 mild or moderate joint BEs treated, 135 were target joint bleeds (in 15 subjects) and 261 were non-target joint bleeds (in 25 subjects). At 12 hours post-initial infusion, target joint treatment success proportions and 95% confidence intervals (CIs) were 82% (95% CI: [63%, 100%]) and 93% (95% CI: 82%, 100%]) in the 75 and 225 µg/kg IDRs, respectively (Figure 1). Corresponding success proportions and CIs for non-target joint bleeds were 86% (95% CI: [75%, 97%]) and 95% (95% CI: [90%, 100%]), respectively. The increase in treatment success proportion observed at 12 hours with the 225 µg/kg IDR over the 75 µg/kg IDR was statistically significant for both target joint and non-target joint groups (p < 0.05). For both IDRs, the difference in treatment success proportions between target and non-target joint BEs was not statistically significant. Nearly all target (97-100%) and non-target joint bleeds (96-100%) were successfully treated at 24 hours post-initial eptacog beta infusion in each IDR (Figure 1). Conclusions The increase in both target and non-target joint bleed treatment success seen at 12 hours for the 225 µg/kg IDR over the 75 µg/kg IDR was statistically significant, and is consistent with a dose-dependent thrombin burst driving effective clot formation at the site of injury. While the 75 µg/kg IDR may be appropriate for certain patients, the 225 µg/kg IDR shows improved treatment success at 12 hours and may be the preferred choice in most circumstances. With the high efficacy seen at 24 hours, eptacog beta offers an important treatment option for treating both target and non-target joint BEs in PwHABI. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clot Waveform Analysis for Monitoring Hemostasis.

Clot waveform analysis (CWA) is a recently developed global coagulation assessment, based on the continuous observation of changes in light transmittance, absorbance, or light scattering that occurs as fibrin formed in a plasma sample during routine clotting tests such as activated partial thromboplastin time (aPTT) and prothrombin time (PT). CWA can utilize qualitative waveform patterns as well as sensitive quantitative parameters and can be used as a simple method to assess global hemostasis, and can be applied to various challenging clinical situations. Although not all coagulation analyzers currently in use are able to provide CWA, the number of analyzers available to do so is increasing, as the usefulness of this process has become more widely recognized. CWA can be based on the coagulation mechanism of aPTT, an intrinsic trigger, and this has been reported in many studies, including diagnosis and treatment of patients with hemophilia, disseminated intravascular coagulation, and monitoring of anticoagulants and thrombosis. CWA using trace amounts of tissue factors also has the potential to expand the applications of this technology. Recently, there have been reports of the combined evaluation of fibrinolytic dynamics. Among the existing global coagulation assays, CWA may prove to be the easiest to standardize in clinical practice. However, more extensive testing using standardized methods in various clinical settings is needed to determine the true role of CWA in the evaluation of hemostasis and thrombosis in the future.

The Design and Feasibility of the: Radial Artery Puncture Hemostasis Evaluation - RAPHE Study, a Prospective, Randomized, Multicenter Clinical Trial.

Introduction and AimRadial artery approach angiography is the current gold standard for coronary status diagnostics and eventual percutaneous revascularization (PCI). Currently, application of adequate, patent hemostasis based physical torniquets are used for puncture site control, to avoid bleeding, radial artery occlusion and damage (RAO and RAD). The Radial Artery Puncture Hemostasis Evaluation (RAPHE) is a prospective, randomized, multicenter clinical trial designed to investigate new, simplified techniques of radial artery hemostasis utilizing physical compression free methods.Methods and ResultsThe RAPHE study has been designed to evaluate the efficacy and safety of two non-compression based radial artery hemostasis methods: a 100% chitosan bioactive hemostatic dressing and a purpose-built radial potassium-ferrate based topical hemostasis disc. These devices will be investigated in a standalone configuration. Control group is a standard pneumatic airbladder-based compression device. A total of 600 patients will be enrolled in a three-way randomization (1:1:1) with two study and one control groups. Safety and efficacy endpoints are RAO, puncture site hematoma formation and RAD respectively, consisting of dissection, (pseudo)aneurism and/or fistula formation, measured post-procedure and at sixty days.ConclusionThe results from this trial will provide valuable information on new, simplified methods of radial artery hemostasis options and possibly simplify post-puncture management of patients.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT04857385].

Hemostasis and oxidative stress in chronic kidney disease in children and adolescents.

Chronic kidney disease (CKD) can be defined as the progressive loss of renal function, characterized by a decreased glomerular filtration rate (GFR). The etiology of CKD in childhood is mainly associated with congenital anomalies of the kidneys and urinary tract (CAKUT) and with glomerular diseases. The goal of this study was to investigate the hemostasis and oxidative stress in pediatric CKD of different etiologies. Fifty-four CKD children and adolescents and 52 controls were enrolled in this study. The evaluation of hemostasis was carried out by determination of D-dimer (D-Di) and plasminogen activator inhibitor (PAI-1) plasma levels, while oxidative stress was evaluated by thiobarbituric acid reactive substance (TBARS) levels, protein carbonyl content, plasma antioxidant capacity (MTT), and ascorbate. The D-Di was increased in CAKUT stage 3 or 4 patients compared with those with glomerular disease. PAI-1 was increased in patients with glomerular disease compared with CAKUT. Carbonyl protein content was higher in the control group compared with glomerular disease stage 3 or 4 patients. Our findings showed that the reduction in GFR is associated with a state of hypercoagulability. The analysis of integrated networks showed an expansion of connections among hemostatic and oxidative stress markers in CKD children and adolescents compared with controls.

Assessment of Hemostasis

Hemostasis is the collection of biological mechanisms responsible for bleeding cessation following surgical procedures or trauma. Congenital and acquired disorders affecting any element of the hemostatic system can result in a spectrum of bleeding pathologies ranging from inability to form stable blood clot to the pathologic propagation of blood clot outside the area of injury. Assessing the hemostatic system in an accurate and timely fashion is critical for detection of these disorders. This review briefly covers the mechanisms of primary and secondary hemostasis before comprehensively exploring the approach to preoperative evaluation of hemostasis, the strengths and weaknesses of commonly used laboratory tests of coagulation, the interpretation of test results, and the management of patients found to have abnormal hemostatic systems. Figures detail the mechanisms of hemostasis and the important features of viscoelastic testing. Tables explain the parameters frequently measured in viscoelastic testing and propose potential treatment plans based on test findings. This review contains 5 figures, 9 tables and 72 references Keywords: coagulation, conventional coagulation tests, hemostasis, thromboelastography, thromboelastometry

Assessment of Hemostasis

Hemostasis is the collection of biological mechanisms responsible for bleeding cessation following surgical procedures or trauma. Congenital and acquired disorders affecting any element of the hemostatic system can result in a spectrum of bleeding pathologies ranging from inability to form stable blood clot to the pathologic propagation of blood clot outside the area of injury. Assessing the hemostatic system in an accurate and timely fashion is critical for detection of these disorders. This review briefly covers the mechanisms of primary and secondary hemostasis before comprehensively exploring the approach to preoperative evaluation of hemostasis, the strengths and weaknesses of commonly used laboratory tests of coagulation, the interpretation of test results, and the management of patients found to have abnormal hemostatic systems. Figures detail the mechanisms of hemostasis and the important features of viscoelastic testing. Tables explain the parameters frequently measured in viscoelastic testing and propose potential treatment plans based on test findings. Key words: coagulation; conventional coagulation tests; hemostasis; thromboelastography; thromboelastometry

Iridoid Glycosides from Phlomis Medicinalis Diels: Optimized Extraction and Hemostasis Evaluation.

Phlomis medicinalis Diels, an important perennial herbal plant unique to the Qinghai-Tibet Plateau, is often used as Tibetan Materia Medicine Radix Phlomii for the treatment of cold, cough, and convergence trauma. In order to efficiently extract the iridoid glycosides from P. medicinalis, an ultrasound-assisted deep eutectic solvent extraction technique was employed. The main parameters influencing the extraction process were studied through single-factor tests and the extraction was optimized by using response surface methodology. The hemostasis activity of total iridoid glycosides (TIG) from P. medicinalis was evaluated in vitro and in mice. The optimization results revealed that the optimal process parameters were liquid-solid ratio 20 : 1, choline chloride-lactic acid concentration 79 %, and sonication time 34 min, under which a TIG extraction yield of 20.73 % was obtained. Meanwhile, high-performance liquid chromatography-photodiode array/mass spectrometry (HPLC-PDA/MS) was employed to characterize the optimized extract and indicated that TIG from P. medicinalis mainly consisted of sixteen reported iridoid glycosides with a total content of 91.22 %. The experimental results in vivo and in vitro indicated that TIG from P. medicinalis had strong hemostasis activities, which may be achieved by increasing the fibrinogen levels. Therefore, the ultrasound-assisted deep eutectic solvent extraction is an effective method to extract iridoid glycosides from P. medicinalis and they will be promising candidates to be developed for medical hemostasis agents.

WHOLE BLOOD THROMBOELASTOGRAPHY IN HEALTHY ADULT CAMELIDS (VICUGNA PACOS AND CAMELUS DROMEDARIUS).

Thromboelastography (TEG) provides a global assessment of hemostasis and fibrinolysis and has broad applications to identify and monitor coagulation dysfunction in veterinary patients. Although alpacas are susceptible to a wide variety of coagulopathies, the assessment of TEG has not been reported in clinically healthy alpacas to date. The purpose of this study was to evaluate the analytical performance of recombinant human tissue factor (rhTF)- and kaolin-activated TEG and to establish reference intervals for TEG parameters (reaction [R] and clotting [K] times, angle [α], maximum amplitude [MA], and shear elastic modulus [G]) in healthy, adult alpacas. Kaolin and rhTF-activated TEG were performed using citrated whole blood samples from 20 clinically healthy, nonpregnant, adult Huacaya alpacas each after 30 min of sample storage at room temperature. Six individuals of a related species, dromedary camels, were also sampled for comparative purposes. All data were presented descriptively, assessed for normality, and compared using either independent-sample t tests or Mann-Whitney U tests, with P ≤ 0.05 considered significant. Reference intervals were calculated using a robust method and Box-Cox-transformed data. Mean TEG values (reference intervals) were determined for rhTF-activated TEG as follows: R 6.99 min (3.41-12.71), K 3.43 min (1.61-6.42), α 48.51° (27.21-67.38), MA 52.05 mm (21.53-65.92), and G 5.71 kdyn/cm2 (1.87-9.60), while mean values (reference intervals) for kaolin-activated TEG included R 7.72 min (4.48-11.43), K 4.24 min (2.03-9.20), α 45.06° (23.66-64.20), MA 52.18 mm (33.49-66.63), and G 5.78 kdyn/cm2 (NR-9.66). None of the measured TEG values differed significantly between activators, suggesting that activator choice may have a limited effect on TEG parameters in healthy alpacas. TEG results in alpacas were comparable to those of dromedary camels. These results will thus provide a useful starting point in the evaluation of hemostasis in adult camelids.